Umbilical Cord Lining Stem Cells as a Novel and Promising Source for Ocular Surface Regeneration

Abstract

The stem cells involved in renewal of the corneal epithelium are located in the basal region of the limbus, a narrow transition zone surrounding the cornea. In many ocular surface disorders loss of these stem cells results in partial or complete vision loss. Conventional corneal transplant in these patients is associated with dismal results. Stem cell transplantation offers new hope to such patients. The umbilical cord is emerging as an important source of stem cells that may have potential clinical applications. There are advantages to the use of umbilical cord stem cells as these cells are less immunogenic, non-tumorigenic, highly proliferative and ethically acceptable. In this study, we have confirmed the expression of several putative limbal stem cell markers such as HES1, ABCG2, BMI1, CK15 as well as cell adhesion-associated molecules INTEGRIN-α6, -α9, -β1, COLLAGEN-IV and LAMININ in our recently characterized CLEC-muc population derived from human umbilical cord. Ex vivo expansion of these cells on a human amniotic membrane substrate formed a stratified cell sheet that similarly expresses some of these molecules as well as cornea-specific cytokeratins, CK3 and CK12. Transplantation of a bioengineered CLEC-muc sheet in limbal stem cell-deficient rabbit eyes resulted in regeneration of a smooth, clear corneal surface with phenotypic expression of the normal corneal-specific epithelial markers CK3, CK12 but not CK4 or CK1/10. Our results suggest that CLEC-muc is a novel stem cell that can be ex vivo expanded for corneal epithelial regeneration in the treatment of various eye diseases.

Ocular surface reconstruction using stem cell and tissue engineering

“…In an aim to further improve these surgical procedures, many groups worldwide have tried to develop treatments that use novel cell sources such as embryonic stem cells (Homma et al, 2004), mesenchymal stem cells , epidermal stem cells , immature dental-pulp stem cells (Monteiro et al, 2009), hair follicle bulge-derived stem cells (Meyer-Blazejewska et al, 2011) and umbilical cord stem cells (Reza et al, 2011). Most recently, we reported an attempt to overcome the problems of treating severe OSD with the most severe dry eye by transplanting a tissue-engineered cultivated nasal mucosal epithelial cell sheet to supply functional goblet cells and to stabilize and reconstruct the ocular surface (Kobayashi et al, 2015).…”

Mesenchymal stem cells: Potential role in corneal wound repair and transplantation

“…MSCs have been isolated from several adult tissues, including the liver, dental pulp, adipose tissue, endometrium, muscle, amniotic fluid, placenta, and umbilical cord blood [12][13][14] . MSCs isolated from bone marrow [16] , umbilical cord [17] , and adipose tissue [18] promote regeneration and corneal wound repair. In addition, MSCs exist in the perivascular niche of several tissues, including the skeletal muscle and pancreas [19] .…”

Progenitor Cells for Ocular Surface Regenerative Therapy

“…Umbilical cord stem cells have a high proliferative potential, are less immunogenic and nontumorigenic and can be obtained by minimally invasive methodologies [52]. Recently, the expression of several putative markers found in human LSCs, such as ABCG2, CK15 and several integrins (α6, α9, β1 subunits), in progenitor cells derived from umbilical cord has been confirmed [53]. In addition, growth and ex vivo expansion on AM showed a stratified cellular arrangement with expression of specific corneal CKs (CK3, CK12), suggesting a therapeutic potential for corneal epithelial regeneration.…”